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Case Reports in Obstetrics and Gynecology

Volume 2017, Article ID 8698670, 3 pages
https://doi.org/10.1155/2017/8698670

Case Report
Previable Preeclampsia Diagnosed by Renal Biopsy in Setting of
Novel Diagnosis of C4 Glomerulopathy

Jessica Parrott,1 Timothy A. Fields,2 and Marc Parrish1

1
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Kansas School of Medicine,
3901 Rainbow Boulevard, Kansas City, KS 66160, USA
2
Department of Pathology and Laboratory Medicine, University of Kansas School of Medicine, 3901 Rainbow Boulevard,
Kansas City, KS 66160, USA

Correspondence should be addressed to Jessica Parrott; jparrott3@kumc.edu

Received 17 April 2017; Accepted 1 June 2017; Published 4 July 2017

Academic Editor: Svein Rasmussen

Copyright © 2017 Jessica Parrott et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background. Preeclampsia diagnosed before 20 weeks’ gestational age is a rare entity, particularly without any predisposing
factors. We report a case of preeclampsia occurring prior to 20 weeks’ gestational age in the setting of a novel diagnosis of
C4 glomerulopathy. Case. A G3P0020 at 18 weeks presented with new onset hypertension and proteinuria, requiring multiple
antihypertensive agents to maintain control. Renal biopsy demonstrated thrombotic microangiopathic lesions and glomerular
endotheliosis. C4-dominant staining and numerous subendothelial and mesangial electron dense deposits were found within the
glomerulus. With no other definable etiologies, preeclampsia was diagnosed. She developed posterior reversible encephalopathic
syndrome and pregnancy termination was recommended. Conclusion. The lectin complement pathway may play a role in the
pathophysiology of severe, early onset preeclampsia. Renal biopsy may play an integral role in diagnosis.

1. Introduction for eclampsia prophylaxis. Intermittent intravenous antihy-

Preeclampsia is a diagnosis marked by new onset hyperten-
sion and proteinuria with usual onset after 20 weeks’ ges-
tational age. Previable preeclampsia is a rare entity with
most reported cases associated with trophoblastic disease,
triploidy, and antiphospholipid antibody syndrome [1–5].
Only a few published case reports exist describing onset
of “pure” preeclampsia, with no identifiable predisposing
factors other than advanced maternal age, at less than 20
weeks [6, 7]. We report a case of previable preeclampsia
occurring prior to 20 weeks’ gestation in a patient with a novel
diagnosis of C4 glomerulopathy.
2. Case Report
A 27-year-old, gravida 3 para 0020, was transferred to our
institution at 18 weeks’ gestational age with new onset severe
hypertension (blood pressure > 180/100 mmHg) and >10 g of
protein on spot urine. Upon arrival to the labor and delivery
unit, she was started on intravenous magnesium sulfate
pertensive treatment was required for severe hypertension
(blood pressure > 160/105 mmHg) but she was overall con-
trolled with oral labetalol and nifedipine. Her 24-hour urine
protein was 8822 mg. Her serum labs were unremarkable with
a hemoglobin of 10.6 gm/dL, platelet count of 183 K/UL, cre-
atinine of 0.6 mg/dL, AST/ALT of 24/15 U/L, and uric acid of
4.4 mg/dL. Nephrology was consulted and an extensive work-
up was done. A low complement C4 of <8.0 was found. The
patient, otherwise, had a negative renal ultrasound, antiphos-
pholipid antibody studies, antinuclear antibody, C-ANCA/P-
ANCA, myeloperoxidase antibody, serine protease 3 anti-
body, glomerular basement membrane antibody, viral hepati-
tis panel, thyroid stimulating hormone (TSH), and urine drug
screening. Due to concern for preexisting renal pathology, the
decision was made to proceed with a renal biopsy.
Initial light microscopy findings were consistent with a
thrombotic microangiopathic lesion, compatible with pree-
clampsia. On review with the pathologist, the main find-
ing was glomerular endotheliosis and glomerular capillary
2 Case Reports in Obstetrics and Gynecology
(a)
Figure 1: Some key renal biopsy findings. (a) PAS-stained section showed (arrows) duplication of glomerular basement membranes
and endotheliosis (PAS stain; bar = 50 𝜇m). (b) Immunohistochemical stain demonstrated C4d deposition within glomerular capillaries
(highlighted by arrowheads). (c) Electron microscopy demonstrated conspicuous subendothelial electron dense deposit (arrow).
double contours (Figure 1). There was no artery or arteri-
ole involvement and there was no thrombi or red blood
cell fragmentation. Immunofluorescence microscopy showed
weak (1+) segmental glomerular staining for IgM and C1q
and no staining for IgG, IgA, C3, or 𝜅 or 𝜆 light chains.
The biopsy findings, the new onset severe hypertension, and
new onset nephrotic range proteinuria in the absence of any
other definable etiology led us to the eventual diagnosis of
preeclampsia.
After a few days, the patient began to develop worsen-
ing hypertension despite being on increasing doses of oral
labetalol and nifedipine, requiring additional intravenous
antihypertensives for breakthrough severe range blood pres-
sures. She also developed persistent neurologic symptoms
consistent with posterior reversible encephalopathic syn-
drome. Her serum labs, including creatinine, remained stable.
Due to the severe nature of her preeclampsia at a previable
gestational age, pregnancy termination was recommended.
Within 6 hours of the patient’s delivery, she no longer
required intravenous antihypertensive therapy. Her neuro-
logic symptoms resolved within 72 hours of delivery. She
had a follow-up visit with nephrology 17 days after delivery
and her urinalysis demonstrated no protein. Her serum labs
at that time included hemoglobin of 12.0 gm/dL, platelet
count of 307 K/UL, creatinine of 0.74 mg/dL, and AST/ALT
of 25/17 U/L.
Following her delivery, electron microscopic examination
of the biopsy revealed numerous subendothelial and mesan-
gial electron dense deposits within the glomerulus. Subse-
quent immunostain for C4d demonstrated intense staining
of the glomerular capillaries. These findings were felt to be
consistent with C4 glomerulopathy.
3. Comment
Preeclampsia is generally thought of as a disease that develops
after 20 weeks’ gestation; however, case reports have been
published describing onset prior to the 20 weeks. There
have been 4 cases described in the setting of pregnancy
complicated by trophoblastic disease or triploidy, as well
as one case complicated by antiphospholipid antibody syn-
drome [1–5]. Two additional cases, in women of advanced
(b) (c)
maternal age, have been described—being coined “pure”
preeclampsia due to the lack of any identifiable etiology
or predisposing factor. In both cases, the women had a
history of preeclampsia in a prior pregnancy and one of
the women had known chronic hypertension [6, 7]. These
unique cases present many challenges as we must consider all
diagnostic possibilities—such as lupus nephritis, hemolytic-
uremic syndrome, antiphospholipid antibody syndrome, or
thrombotic thrombocytopenic purpura [8]. In these difficult
scenarios, renal biopsy can be a safe and useful tool in
identifying the correct diagnosis and guiding appropriate
management.
On renal biopsy, the most common pathologic findings
in preeclampsia include endotheliosis, podocyte vacuolation,
mesangial cell proliferation, and renal tubule protein casts;
in addition, immunofluorescence microscopy is commonly
positive for multiple complement components (C3, C1q, and
C4d) and immunoglobulins (usually IgM) [9]. The findings of
C4-dominant staining and numerous electron dense deposits
in this case were unusual. A recently published article
described 3 patients with similar findings and proposed
a novel diagnosis for this entity, C4 glomerulopathy [10].
The presence of glomerular C4d, a split product of C4, is
indicative of C4 activation, which can occur as a result of
activation of either the classical complement pathway or
the lectin pathway. Immune complex glomerulonephritides
(e.g., lupus) often activate the classical pathway activation
by the binding of C1q to the antibody-containing immune
complexes, which can result in glomerular deposition of
immunoglobulins, C3, C1q, and C4d. In the lectin pathway,
lectin proteins bind to sugars (mannose) located on the
microbial membranes or carbohydrate structures, which in
turn activate C4 and bypass C1q activation [10]. In C4
glomerulopathy, the presence of bright C4d and negative
or minimal staining for immunoglobulins, C1q, and C3 is
suggestive of a lectin pathway abnormality [11]. The question
is as follows: How does the lectin pathway get activated?
The currently proposed theories have included genetic
factors, acquired autoantibodies, or even a paraprotein that
interferes with the lectin pathway that may play a role in the
development of C4 glomerulopathy [9, 12]. Lectin pathway
activation has been demonstrated in some immune complex
Case Reports in Obstetrics and Gynecology
glomerular diseases, including poststreptococcal glomeru-
lonephritis and IgA nephropathy, though those diseases have
a very different microscopic appearance. In line with these
proposed mechanisms, an extensive work-up was done in
this patient to determine whether there were any underlying
processes present that would have led to abnormal activation
of the lectin pathway or other channels in the complement
pathway. As part of this work-up she had negative screening
for immune and infectious etiologies, in addition to a normal
serum protein electrophoresis, a negative paraprotein analy-
sis, and normal light chain analysis. We also assessed different
components of her complement system including C3 and
Factor H and Factor B levels, which were all normal. Her
serum C4 level, which was low during the time of her initial
disease presentation, normalized three weeks after her deliv-
ery. If it is not a preexisting entity, then one may speculate
that there is a component of pregnancy and/or a mechanism
of preeclampsia that activates the lectin complement pathway.
To our knowledge, there are only four other known cases
of a pregnancy being complicated by C4 glomerulopathy,
and unfortunately the current status of the patients and the
outcomes of any subsequent pregnancies are unknown [9,
10, 13]. With little known information on the physiology and
mechanism of lectin complement pathway activation, it is
difficult to counsel the patient on risk of recurrence of such
an adverse pregnancy outcome in a subsequent pregnancy.
Using the best available data, we quoted a recurrence risk of
50–60% but also emphasized that there was approximately a
30% chance that the disease onset could be prior to 28 weeks’
gestational age [14–16].
Conflicts of Interest
The authors declare that there are no conflicts of interest
regarding the publication of this paper.
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